RESUMEN
In this work, two novel chalcone-based imidazothiazole derivatives ITC-1 and ITC-2 were synthesized and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry with electrospray ionization, and chemical structure of ITC-1 was confirmed by single-crystal X-ray diffraction. Also, the anticancer activity of ITC-1 and ITC-2 was evaluated. First, antiproliferative activity tests were performed against cancer cells namely, human-derived breast adenocarcinoma (MCF-7), lung carcinoma (A-549), and colorectal adenocarcinoma (HT-29) cell lines, and mouse fibroblast healthy cell line (3T3-L1) by XTT assay. Afterward, mitochondrial membrane disruption (MMP), caspase activity, and apoptosis tests were performed on MCF-7 cells to elucidate the anticancer mechanism of action of the test compounds by flow cytometry analysis. XTT results revealed that both compounds exhibited a very high degree of antiproliferative effects on each tested cancer cell line with very low IC50 values while showing much lower antiproliferation on 3T3-L1 normal cells with much higher IC50 values. Besides, ITC-2 was determined to have a striking cytotoxic power competing with the chemotherapeutic drug carboplatin. Flow cytometry results demonstrated the mitochondrial-mediated apoptotic effects of both compounds through membrane disruption and multi-caspase activation in MCF-7 cells. Finally, molecular docking studies were performed to determine the structural understanding of the test compounds by their interactions on caspase-3 and DNA dodecamer enzymes, respectively. The interactions between the compound and the crystal structure were determined according to parameters such as free binding energies (ΔGBind), Glide score values, and determination of the active binding site. The obtained data suggest that ITC-1 and ITC-2 may be considered remarkable anticancer drug candidates. In addition to molecular docking via in silico approaches, the pharmacokinetic properties of compounds ITC-1 and ITC-2 were calculated using the Schrödinger 2021-2 Qikprop wizard.Communicated by Ramaswamy H. Sarma.
RESUMEN
The title compound, C22H15N3O4, is built up from a central imidazo[1,2-a]pyridine ring system connected to a nitroso group, a phenyl ring and a 2-oxo-2-phenyl-ethyl acetate group. The imidazo[1,2-a] pyridine ring system is almost planar (r.m.s. deviation = 0.017â Å) and forms dihedral angles of 22.74â (5) and 45.37â (5)°, respectively, with the phenyl ring and the 2-oxo-2-phenyl-ethyl acetate group. In the crystal, the mol-ecules are linked into chains parallel to the b axis by C-Hâ¯O hydrogen bonds, generating R 2 1 (5) and R 4 4 (28) graph-set motifs. The chains are further linked into a three-dimensional network by C-Hâ¯π and π-stacking inter-actions. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing that the most important contributions for the crystal packing are from Hâ¯H (36.2%), Hâ¯C/Câ¯H (20.5%), Hâ¯O/Oâ¯H (20.0%), Câ¯O/Oâ¯C (6.5%), Câ¯N/Nâ¯C (6.2%), Hâ¯N/Nâ¯H (4.5%) and Câ¯C (4.3%) inter-actions.
RESUMEN
In the mol-ecular structure of the title compound, C20H21N3O7, the quinoline ring system is slightly bent, with a dihedral angle between the phenyl and the pyridine rings of 3.47â (7)°. In the crystal, corrugated layers of mol-ecules extending along the ab plane are generated by C-Hâ¯O hydrogen bonds. The inter-molecular inter-actions were qu-anti-fied by Hirshfeld surface analysis and two-dimensional fingerprint plots. The most significant contributions to the crystal packing are from Hâ¯H (42.3%), Hâ¯O/Oâ¯H (34.5%) and Hâ¯C/ Câ¯H (17.6%) contacts. Mol-ecular orbital calculations providing electron-density plots of the HOMO and LUMO as well as mol-ecular electrostatic potentials (MEP) were computed, both with the DFT/B3LYP/6-311â G++(d,p) basis set. A mol-ecular docking study between the title mol-ecule and the COVID-19 main protease (PDB ID: 6LU7) was performed, showing that it is a good agent because of its affinity and ability to adhere to the active sites of the protein.
RESUMEN
Two polymorphs of the title compound, C19H16N2O3, were obtained from ethano-lic (polymorph I) and methano-lic solutions (polymorph II), respectively. Both polymorphs crystallize in the monoclinic system with four formula units per cell and a complete mol-ecule in the asymmetric unit. The main difference between the mol-ecules of (I) and (II) is the reversed position of the hy-droxy group of the carb-oxy-lic function. All other conformational features are found to be similar in the two mol-ecules. The different orientation of the OH group results in different hydrogen-bonding schemes in the crystal structures of (I) and (II). Whereas in (I) inter-molecular O-Hâ¯O hydrogen bonds with the pyridazinone carbonyl O atom as acceptor generate chains with a C(7) motif extending parallel to the b-axis direction, in the crystal of (II) pairs of inversion-related O-Hâ¯O hydrogen bonds with an R 2 2(8) ring motif between two carb-oxy-lic functions are found. The inter-molecular inter-actions in both crystal structures were analysed using Hirshfeld surface analysis and two-dimensional fingerprint plots.
RESUMEN
The title pyridazinone derivative, C20H18N2O3, is not planar. The phenyl ring and the pyridazine ring are inclined to each other by 10.55â (12)°, whereas the 4-methyl-benzyl ring is nearly orthogonal to the pyridazine ring, with a dihedral angle of 72.97â (10)°. In the crystal, mol-ecules are linked by pairs of O-Hâ¯O hydrogen bonds, forming inversion dimers with an R 2 2(14) ring motif. The dimers are linked by C-Hâ¯O hydrogen bonds, generating ribbons propagating along the c-axis direction. The inter-molecular inter-actions were additionally investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots. They revealed that the most significant contributions to the crystal packing are from Hâ¯H (48.4%), Hâ¯O/Oâ¯H (21.8%) and Hâ¯C/Câ¯H (20.4%) contacts. Mol-ecular orbital calculations providing electron-density plots of HOMO and LUMO mol-ecular orbitals and mol-ecular electrostatic potentials (MEP) were also computed, both with the DFT/B3LYP/6-311â G++(d,p) basis set.
RESUMEN
The asymmetric units of the title compounds both contain one nonplanar mol-ecule. In 4-benzyl-6-phenyl-4,5-di-hydro-pyridazin-3(2H)-one, C17H14N2O, (I), the phenyl and pyridazine rings are twisted with respect to each other, making a dihedral angle of 46.69â (9)°; the phenyl ring of the benzyl group is nearly perpendicular to the plane of the pyridazine ring, the dihedral angle being 78.31â (10)°. In methyl 2-[5-(2,6-di-chloro-benz-yl)-6-oxo-3-phenyl-1,4,5,6-tetra-hydropyridazin-1-yl]acetate, C20H16Cl2N2O3, (II), the phenyl and pyridazine rings are twisted with respect to each other, making a dihedral angle of 21.76â (18)°, whereas the phenyl ring of the di-chloro-benzyl group is inclined to the pyridazine ring by 79.61â (19)°. In the crystal structure of (I), pairs of N-Hâ¯O hydrogen bonds link the mol-ecules into inversion dimers with an R 2 2(8) ring motif. In the crystal structure of (II), C-Hâ¯O hydrogen bonds generate dimers with R 1 2(7), R 2 2(16) and R 2 2(18) ring motifs. The Hirshfeld surface analyses of compound (I) suggests that the most significant contributions to the crystal packing are by Hâ¯H (48.2%), Câ¯H/Hâ¯C (29.9%) and Oâ¯H/Hâ¯O (8.9%) contacts. For compound (II), Hâ¯H (34.4%), Câ¯H/Hâ¯C (21.3%) and Oâ¯H/Hâ¯O (16.5%) inter-actions are the most important contributions.
RESUMEN
In the title com-pound, C13H14N2O3, the dihydropyridazine ring (r.m.s. deviation = 0.166â Å) has a screw-boat conformation. The dihedral angle between its mean plane and the benzene ring is 0.77â (12)°. In the crystal, inter-molecular O-Hâ¯O hydrogen bonds generate C(5) chains and N-Hâ¯O hydrogen bonds produce R 2 2(8) motifs. These types of inter-actions lead to the formation of layers parallel to (12). The three-dimensional network is achieved by C-Hâ¯O inter-actions, including R 2 4(8) motifs. Inter-molecular inter-actions were additionally investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots. The most significant contributions to the crystal packing are by Hâ¯H (43.3%), Hâ¯C/Câ¯H (19.3%), Hâ¯O/Hâ¯O (22.6%), Câ¯N/Nâ¯C (3.0%) and Hâ¯N/Nâ¯H (5.8%) contacts. C-Hâ¯π inter-actions and aromatic π-π stacking inter-actions are not observed.
RESUMEN
In this paper, we describe the synthesis of a new di-hydro-2H-pyridazin-3-one derivative. The mol-ecule, C18H16N2O, is not planar; the benzene and pyridazine rings are twisted with respect to each other, making a dihedral angle of 11.47â (2)°, and the toluene ring is nearly perpendicular to the pyridazine ring, with a dihedral angle of 89.624â (1)°. The mol-ecular conformation is stabilized by weak intra-molecular C-Hâ¯N contacts. In the crystal, pairs of N-Hâ¯O hydrogen bonds link the mol-ecules into inversion dimers with an R 2 2(8) ring motif. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional (2D) fingerprint plots, revealing that the most important contributions for the crystal packing are from Hâ¯H (56.6%), Hâ¯C/Câ¯H (22.6%), Oâ¯H/Hâ¯O (10.0%) and Nâ¯C/Câ¯N (3.5%) inter-actions.
RESUMEN
A novel chalcone, C20H20O, derived from benzyl-idene-tetra-lone, was synthesized via Claissen-Schmidt condensation between tetra-lone and 2,4,6-tri-methyl-benzaldehyde. In the crystal, mol-ecules are linked by C-Hâ¯O hydrogen bonds, producing R 2 2(20) and R 2 4(12) ring motifs. In addition, weak C-Hâ¯π and π-stacking inter-actions are observed. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing that the most important contributions for the crystal packing are from Hâ¯H (66.0%), Hâ¯C/ Câ¯H (22.3%), Hâ¯O/Oâ¯H (9.3%), and Câ¯C (2.4%) inter-actions. Shape-index plots show π-π stacking inter-actions and the curvedness plots show flat surface patches characteristic of planar stacking.
RESUMEN
The title pyridazinone derivative, C21H19ClN2O3, is not planar. The unsubstituted phenyl ring and the pyridazine ring are inclined to each other, making a dihedral angle of 17.41â (13)° whereas the Cl-substituted phenyl ring is nearly orthogonal to the pyridazine ring [88.19â (13)°]. In the crystal, C-Hâ¯O hydrogen bonds generate dimers with R 2 2(10) and R 2 2(24) ring motifs which are linked by C-Hâ¯O inter-actions, forming chains extending parallel to the c-axis direction. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing that the most significant contributions to the crystal packing are from Hâ¯H (44.5%), Câ¯H/Hâ¯C (18.5%), Hâ¯O/Hâ¯O (15.6%), Clâ¯H/Hâ¯Cl (10.6%) and Câ¯C (2.8%) contacts.